ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4352A>G (p.Asp1451Gly)

dbSNP: rs80358671
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000044398 SCV000072411 uncertain significance Hereditary breast ovarian cancer syndrome 2021-01-15 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has been observed in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, in that individual a pathogenic allele was also identified in the BRCA1 gene, which suggests that this c.4352A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 51635). This sequence change replaces aspartic acid with glycine at codon 1451 of the BRCA2 protein (p.Asp1451Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV001022341 SCV001184065 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-09 criteria provided, single submitter clinical testing The p.D1451G variant (also known as c.4352A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4352. The aspartic acid at codon 1451 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV001022341 SCV003850440 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Breast Cancer Information Core (BIC) (BRCA2) RCV000113298 SCV000146413 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2002-06-20 no assertion criteria provided clinical testing

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